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Coordination of RNA modifications in the brain and beyond

Molecular Psychiatry volume 28, pages 2737–2749 (2023)Cite this article

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Abstract

Gene expression regulation is a critical process throughout the body, especially in the nervous system. One mechanism by which biological systems regulate gene expression is via enzyme-mediated RNA modifications, also known as epitranscriptomic regulation. RNA modifications, which have been found on nearly all RNA species across all domains of life, are chemically diverse covalent modifications of RNA nucleotides and represent a robust and rapid mechanism for the regulation of gene expression. Although numerous studies have been conducted regarding the impact that single modifications in single RNA molecules have on gene expression, emerging evidence highlights potential crosstalk between and coordination of modifications across RNA species. These potential coordination axes of RNA modifications have emerged as a new direction in the field of epitranscriptomic research. In this review, we will highlight several examples of gene regulation via RNA modification in the nervous system, followed by a summary of the current state of the field of RNA modification coordination axes. In doing so, we aim to inspire the field to gain a deeper understanding of the roles of RNA modifications and coordination of these modifications in the nervous system.

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Fig. 1: Chemical structures and enzymatic processes of modifications discussed.
Fig. 2: Illustration of the three major types of coordination axes.
Fig. 3: Summary of the interaction of TRMT10A and FTO.
Fig. 4: Summary of the functions of TRMT112.

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Acknowledgements

This work was supported by the National Institutes of Health (R35GM133721 and R01HL160726-01A1 to KFL and T32GM132039 to MCO), the American Cancer Society (RSG-22-064-01-RMC to KFL), the Damon Runyon Innovator Award to KFL, and the June Rothman Scott Biology Summer Research Fellowship to AYC. We would like to thank all members of Kathy Liu lab for their helpful discussions while writing this manuscript, especially Drs. Hui Shen and R. Jordan Ontiveros. Marvin was used for drawing, displaying, and characterizing chemical structures, substructures, and reactions in Fig. 1 (Marvin 22.13, 2022, ChemAxon; https://www.chemaxon.com). Figures 2 through 4 were created with BioRender.

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Author notes

  1. These authors contributed equally: Anthony Yulin Chen, Michael C. Owens.

Authors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Anthony Yulin Chen, Michael C. Owens & Kathy Fange Liu

  2. Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA, 19081, USA

    Anthony Yulin Chen

  3. Graduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Michael C. Owens & Kathy Fange Liu

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AYC and MCO wrote the manuscript. AYC, MCO, and KFL edited the manuscript.

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Correspondence to Kathy Fange Liu.

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Chen, A.Y., Owens, M.C. & Liu, K.F. Coordination of RNA modifications in the brain and beyond. Mol Psychiatry 28, 2737–2749 (2023). https://doi.org/10.1038/s41380-023-02083-2

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